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PubMed2006

The effects of concurrent cannabis use among ecstasy users: neuroprotective or neurotoxic?

The research evidence regarding the potential effects of ecstasy suggests that it may be neurotoxic and that its use is associated with cognitive impairment. In recent years evidence has emerged suggesting that cannabinoids, the active ingredients in cannabis, can be neuroprotective under certain conditions. Given that many ecstasy users also consume cannabis at the same time, the possibility emerges that these individuals might be less susceptible to ecstasy-related impairment. The present paper reanalyses the data from a number of previous studies, contrasting the performance of those individuals who generally consume cannabis and ecstasy at the same time with those who generally consume ecstasy on its own. The two ecstasy-using groups are compared with non-ecstasy users on a range of measures including processing speed, random letter generation, verbal and visuo-spatial working memory span, reasoning and associative learning. The two ecstasy user groups did not differ significantly from each other on any of the measures. Both user groups were significantly worse than non-ecstasy users on measures of associative learning, verbal and visuo-spatial working memory and reasoning. The results suggest that consuming cannabis at the same time as ecstasy does not reduce the likelihood of cognitive impairment.

Age Factors↗

PubMed2006

Characterizing behavioral and cognitive dysexecutive changes in progressive supranuclear palsy.

Frontal lobe dysfunction is a prominent feature of many neurological disorders. Early diagnosis may be enhanced by establishing a profile of cognitive, behavioral, and emotional change. Traditional psychometric assessment focuses on cognitive dysfunction and fails to identify behavioral changes, particularly those associated with orbitofrontal dysfunction. We examined progressive supranuclear palsy (PSP), a prototypical subcortical dementia with frontal features, using commonly available neuropsychological measures and a modification of the Katz Adjustment Scale-Relatives (KAS-R), an instrument first developed to assess dysexecutive changes in head-injured patients. Executive tests identified deficits in reasoning, planning, set shifting, verbal fluency, information processing speed, and response initiation. On the KAS-R, changes in apathy, social withdrawal, and independence were observed, with little change in belligerence, social irresponsibility, uncooperativeness, obstreperousness, anxiety, and depression. The results show the potential utility of this instrument in characterizing behavioral and emotional changes associated with frontal lobe dysfunction in neurodegenerative disease.

Affective Symptoms↗

PubMed2006

Neuropsychological profile of DYT1 dystonia.

The common belief that primary dystonia is a purely motor disorder has recently been challenged. We examined separately the cognitive profiles of symptomatic (SYM) and nonsymptomatic (N-SYM) groups of carriers of DYT1 mutation using a comprehensive neuropsychological test battery. Self-report inventories of anxiety, depression, and pain levels were also administered, as well as manual motor dexterity assessment. Each group was matched with healthy controls by age, sex, mother tongue, and education. No significant differences between the SYM group to its control group were found on cognitive tests evaluating verbal and nonverbal abstract abilities, attention, information processing speed, and spatial organization. However, the SYM group showed increased verbal memory retroactive interference. Interestingly, the patients also showed higher semantic fluency performance. No significant differences between the N-SYM group to controls were found. It was concluded that symptomatic DYT1 mutation carriers do not suffer the distinctive cognitive decline that is seen in other primary degenerative extrapyramidal disorders.

Adult↗

PubMed2004

Phenotypic variation and FMRP levels in fragile X.

Data on the relationships between cognitive and physical phenotypes, and a deficit of fragile X mental retardation 1 (FMR1) gene-specific protein product, FMRP, are presented and discussed in context with earlier findings. The previously unpublished results obtained, using standard procedures of regression and correlations, showed highly significant associations in males between FMRP levels and the Wechsler summary and subtest scores and in females between these levels and the full-scale intelligence quotient (FSIQ), verbal and performance IQ, and some Wechsler subtest scores. The published results based on data from 144 extended families with fragile X, recruited from Australia and the United States within a collaborative NIH-supported project, were obtained using robust modification of maximum likelihood in pedigrees. The results indicated that processing speed, short-term memory, and the ability to control attention, especially in the context of regulating goal-directed behavior, may be primarily affected by the FMRP depletion. The effect of this depletion on physical phenotype was also demonstrated, especially on body and head height and extensibility of finger joints. It is recommended that further studies should rely on more accurate measures of FMRP levels, and use of larger samples, to overcome extensive variability in the data.

Cognition Disorders↗

PubMed1998

Automated high-throughput mass spectrometric analysis of synthetic oligonucleotides.

The use of automated sample preparation and data collection coupled with delayed ion extraction matrix-assisted laser desorption ionization with time-of-flight detection mass spectrometry (DE MALDI-TOF MS) enables the rapid mass analysis of oligonucleotide samples. We have incorporated a matrix-diluting and liquid-spotting automated work station and a DE MALDI mass spectrometer to provide high-throughput analysis of synthetic oligonucleotides. Automated sample preparation greatly speeds processing while the spotting function allows for precise sample placement on a 100-well sample plate. The DE MALDI MS typically determines the mass of each sample to within 0.13 +/- 0.10% of the theoretically expected mass. This mass accuracy allows confirmation of identity and detection of low-level impurities present in synthetic oligonucleotide samples with an unprecedented degree of confidence. Using this automation suite, sample preparation, spotting, and analysis of 100 samples ranging from 12 to 70 bases in length can be routinely completed in less than 90 min.

Calibration↗

PubMed2000

Impaired frontostriatal cognitive functioning following posteroventral pallidotomy in advanced Parkinson's disease.

We investigated the long-term effects of posteroventral pallidotomy on tests sensitive to the functional integrity of frontostriatal neural systems in a sample of 11 patients with advanced Parkinson's disease (PD). Patients were assessed within 1 month prior to surgery and at 12 months following pallidotomy. Changes in outcome measures were compared to a control sample of equally performing PD patients receiving nonsurgical medical management assessed over a 12-month period. Measures of cognitive abilities sensitive to frontostriatal functional integrity tested psychomotor processing speed, executive components of working memory, and reasoning. Additional tests of general mental status and semantic memory ability were utilized to assess the specificity of the effect of pallidotomy on cognitive function. Significant declines in performance on all measures sensitive to frontostriatal integrity were found for the surgery group but not the PD control group. No significant changes in performance were found on the measures of general mental status or semantic memory for either the surgery or PD control samples. These results suggest that the posteroventral pallidotomy selectively impairs performance on tests of frontostriatal cognitive abilities.

Adult↗

PubMed1991

Cumulative cognitive impairment following recurrent severe hypoglycaemia in adult patients with insulin-treated diabetes mellitus.

To examine the hypothesis that episodes of severe hypoglycaemia may cause cumulative cognitive impairment. 100 Type 1 (insulin-dependent) diabetic patients were examined. Their age range was 25-52 years, and the onset of diabetes had occurred after the age of 19 years. Patients with evidence of organic brain disease, including cerebrovascular disease, were excluded. A questionnaire was used to assess the number, frequency and severity of hypoglycaemic episodes experienced during treatment with insulin and the accuracy of this retrospective information was verified from general practice and hospital case-notes. A detailed neuropsychological assessment was undertaken, including tests of pre-morbid and present IQ (Wechsler-Revised), memory and information-processing speed. Significant correlations were observed between the frequency of severe hypoglycaemia and the magnitude of intellectual decline, Performance IQ, inspection time and reaction time (patients with the more frequent hypoglycaemia had poorer performance). Two sub-groups of patients were identified on the basis of their experience of severe hypoglycaemia, and were balanced for pre-morbid IQ, age and duration of diabetes. One sub-group (n = 23) had never experienced severe hypoglycaemia (Group A), whilst the other sub-group (n = 24) had suffered at least five episodes of severe hypoglycaemia (Group B). Group B had greater intellectual impairment than Group A, and Group B also had a significantly slower mean reaction time and higher reaction time variance when compared with Group A.

Adult↗

PubMed1992

Amitriptyline, clovoxamine and cognitive function: a placebo-controlled comparison in depressed outpatients.

No longer prescribed only for vegetative signs of depression, tricyclic antidepressants also lessen depressive cognitive distortions. Less clear is whether they ameliorate depressed patients' other cognitive deficits in memory, information processing speed, and psychomotor performance. We tested the alternative hypothesis that amitriptyline, because of its anticholinergic and sedative properties, would exacerbate depressed patients' cognitive disturbances. Depressed outpatients received double-blind placebo (n = 15), amitriptyline (n = 10), or clovoxamine fumarate (n = 10), a serotonin reuptake inhibitor relatively lacking in anticholinergic properties. Depression, memory, and psychomotor performance were assessed at baseline and after 7 and 28 days of drug treatment. Depression was alleviated after all treatments, including placebo. Only amitriptyline impaired performance on tests of memory, producing a significant decrement, relative to placebo, after 4 weeks of treatment. None of the treatments adversely affected performance on psychomotor tasks. These findings add to the evidence that antidepressant drugs with high anticholinergic activity can impair memory, despite alleviation of depression.

Acoustic Stimulation↗

PubMed1996

A randomized trial of visual attention of preterm infants fed docosahexaenoic acid until two months.

This was a randomized, double-blind trial to determine if a nutrient-enriched (preterm) formula supplemented with 0.2% docosahexaenoic acid (DHA, 22:6n-3) from a low eicosapentaenoic acid (0.06%) source of marine oil would enhance visual novelty preference and attention of preterm infants. Both the standard and experimental formulas contained 3% of total fatty acids as linolenic acid (18:3n-3) and were fed from approximately three days of age to two months past term. After two months, both diet groups were fed a commercially-available term formula with linolenic acid as the only source of n-3 fatty acid. At 12 mo visual recognition memory (novelty preference) and visual attention (number and duration of discrete looks) were determined with the Fagan Test of Infant Intelligence. The DHA-supplemented group compared with the control group had more and shorter duration looks in comparisons of familiar and novel stimuli, confirming earlier evidence that DHA can increase information processing speed of preterm infants who otherwise are receiving good intakes of linolenic acid. Because supplementation was stopped at two months and the effects seen at 12 mon, this study demonstrates for the first time that a relatively short period of DHA supplementation can produce significant effects on later visual attention.

Docosahexaenoic Acids↗

PubMed2006

Diversity, dispersion and inconsistency of reaction time measures: effects of age and task complexity.

BACKGROUND AND AIMS: Performance variability of reaction time is regarded as an important parameter for cognitive functioning with aging. We investigated three types of variability, diversity (or variability between persons), dispersion (variability across trials within one task) and inconsistency (variability across testing occasions), while distinguishing between decision time and movement time and evaluating performance across comparable complexity levels. METHODS: A single stratified reaction time test based on tasks with increasing complexity was used to evaluate inter- and intra-performance variability of 27 older (age 75+/-5 years) and 27 younger (age 29+/-7 years) participants, subdividing reaction time into decision and movement components. RESULTS: There were consistent age and complexity differences for all variability types in our sample. When controlling for processing speed, which was slower in the older group, variability across age groups and task complexity tended to diminish and a more complex picture emerged. The elderly group showed a higher diversity of all reaction time measures, except for movement time, and a higher dispersion of decision time. Task complexity significantly affected the diversity of movement and overall reaction times and the dispersion of all reaction time measures, except for movement time. CONCLUSIONS: These results highlight the importance of variability in cognitive functioning; it may be an important phenomenon for study and a useful indicator for cognitive deterioration. The reaction time test we propose is easy to use and can be applied in clinical practice.

Adult↗

PubMed2007

[Effect of subtype and psychiatric comorbidities on methylphenidate treatment in adults with attention-deficit hyperactivity disorder].

The present study was intended to examine the efficacy of immediate-release methylphenidate (MPH IR) in the treatment of adults with attention-deficit hyperactivity disorder (ADHD) under consideration of subtype according to DSM-IV criteria and psychiatric comorbidity. After baseline assessment over 3 weeks, 47 patients aged 18-59 years with combined ADHD (ADHD-C) (n=27) and predominantly inattentive ADHD (ADHD-I; n=20) were treated in an open, uncontrolled design with an average dose of 0.5 mg MPH IR per kg over 7 weeks. Thirty-nine patients finished the study. The two groups did not differ in response to treatment with regard to ADHD symptoms (very good to good outcome in ADHD-C 73.9%, in ADHD-I 66.7%) or cognitive measures (sustained attention, information processing speed, divided attention). However, ADHD patients with psychiatric comorbidities had significantly worse outcome: total ADHS scores on the T2 Brown Attention Deficit Disorder Scales (BADDS) were 66.2+/-15.5 with psychiatric comorbidity and 51.7+/-13.7 without (P=0.04), despite significantly higher doses of MPH IR (0.56+/-0.17 mg/kg vs 0.46+/-0.13 mg/kg; P=0.004). This effect was mainly seen in the patients with clinically significant depressive symptoms (Beck Depression Inventory > or =18), who clearly benefited less from treatment (total T2 BADDS scores with depressive symptoms 70.7+/-15.9 and without depressive symptoms 48.1+/-21.2; P=0.001).

Adolescent↗

PubMed2001

[Cognitive impairments due to add-on therapy with topiramate].

In an open study, 37 epilepsy patients were investigated with regard to cognitive impairments in anticonvulsant add-on therapy with topiramate (TPM). In addition to a preexisting antiepileptic medication, TPM administration was started and increased by 25 mg/week. Cognitive side effects noted by the patient or doctor were assessed by a neuropsychological test battery. In 18/37 patients (49%), cognitive deficits consisting of impaired concentration, psychomotoric slowing, memory deficits, and dysphasia were observed. The adverse effects became apparent at dosages of 50-575 mg TPM/day (average 210 mg). In four patients, they were reversible after reducing the dose of TPM by 25-150 mg/day. In eight patients, the adverse effects led to withdrawal of TPM. In spite of slow titration, the present study showed a higher frequency of cognitive side effects under TPM than was previously reported. In some patients, these side effects led to substantial impairments in daily life and at work. For early recognition of cognitive impairments, neuropsychological baseline and follow-up investigations of verbal fluency, psychomotor processing speed, and verbal memory are recommended.

Adult↗

PubMed2006

Neurodevelopment of children with single suture craniosynostosis: a review.

INTRODUCTION: Rates of neurocognitive risk range from 35-50% of school-aged children with isolated single suture craniosynostosis (SSC). It has been hypothesized that early surgical intervention to release suture fusion reduces risk for increased intracranial pressure (ICP) and the corresponding risk to neurodevelopment. However, studies assessing children with SSC have been inconsistent in finding an association between neurocognitive development, age of surgery, and ICP. REVIEW: SSC produces notable distortion of the cranial vault and underlying brain mass. Although a linear relationship between skull distortion, ICP, and neurocognitive deficits has generally been assumed, recent studies have postulated an interactive process between the skull and developing brain that results in neuroanatomical changes that are not limited to areas directly beneath the fused suture. The specific neuropsychological deficits identified in children with SSC including problems with attention and planning, processing speed, visual spatial skills, language, reading, and spelling may be related to the anatomic differences that persist after correction of suture fusion. CONCLUSIONS: Available literature on neurocognitive development of children with SSC is suggestive of mild but persistent neuropsychological deficits, which become more significant as cognitive demands increase at school age. Anatomical studies of children without SSC are beginning to identify particular groups of brain structures that if disrupted or malformed, may be associated with specific cognitive deficits. Controlled research investigating the relationship between persistent anatomical changes and neurocognitive functioning of school-aged children with SSC is needed.

Adolescent↗

PubMed1999

[Sex differences in morphologic aging processes].

According to Max Bürger (2) it is justified to speak of sexual divergence of biomorphosis. Morphometrical investigations have proved the existence of such sexual differences. The following results were obtained: The first example concerns the increase of fatty tissue in parathyroid glands which we measured on histological slides of 135 human samples by means of the point counting method. The fatty tissue of males was shown to increase continuously with statistic significance, whereas this process stops in females during their generative phase between the 2nd and 5th decade. Evidence for the sexual divergence was also obtained by investigating the fatty tissue between the bundles of muscle fibers of the tongue, however, without being able to statistically verify these results. We found the same sexual differences by measuring the muscle cell regression and connective tissue proliferation in the ciliary muscle of human eyes and tunica muscularis of the small intestine as well. All findings prove that the female is able to stay biologically younger during her generative activity compared to males. After menopause the aging processes speed up in female tissues without making up for the "age lead" of males. It is also worth mentioning that macroscopic anthropometric features do confirm the same fact, e.g., length and breadth of human auricles, ranging in age from 18 to 51 years.

Adipose Tissue↗

PubMed2003

Thalamic stimulation for tremor. Subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect.

The aim of this study was to investigate the impact of unilateral deep brain stimulation (DBS) of the ventrointermediate (Vim) thalamic nucleus on neuropsychological functioning comparing stimulation-on with stimulation-off conditions. Nine patients [five patients with Parkinson's Disease (PD), two patients with essential tremor (ET) and 2 patients with multiple sclerosis (MS)] underwent comprehensive neuropsychological testing for cognitive functions, including general mental impairment, aphasia, agnosia, executive and constructional abilities, learning, memory, cognitive processing speed and attention as well as depression. The neuropsychological assessments were performed at least 6 months postoperatively (mean 9 months). Testing in the stimulation-on and stimulation-off condition was obtained within a period of 3 to 4 weeks. Unilateral DBS resulted in improvement of tremor in all patients. There were no significant differences between the stimulation-on and the stimulation-off condition with the exception of a decrement of word-recall in the short delay free-recall subtest of the Rey Auditory-Verbal Learning Test (RAVLT). Subgroup analysis indicated that the impairment in word-recall was related to left-sided thalamic stimulation. Our study confirms that chronic unilateral DBS is a safe method with regard to cognitive function. The subtle changes in episodic memory are related to stimulation per se and not to a microthalamotomy effect.

Aged↗

PubMed2001

Influence of chronic bilateral stimulation of the subthalamic nucleus on cognitive function in Parkinson's disease.

BACKGROUND: The clinical efficacy of chronic deep brain stimulation in the treatment of parkinsonian patients with severe levodopa-related motor adverse effects has been repeatedly shown. Bilateral subthalamic nucleus (STN) stimulation has been shown to present an advantage over pallidal stimulation as it induces a higher antiakinetic effect and has positive effects on all parkinsonian symptoms. The morbidity of such surgery is usually considered to be very low. However, few studies have extensively examined the effects of chronic STN stimulation on cognitive function. OBJECTIVE: The aim of the present study was to assess the effects of chronic bilateral STN stimulation on performance in an extensive battery of neuropsychological tests, three months and one year after surgery. METHODS: Nine patients with Parkinson's disease were selected for STN electrodes implantation. They underwent a neuropsychological evaluation at one month before and at three months after surgery. Six of them were examined again at one year after surgery. RESULTS: Before surgery, no patient showed cognitive decline. At three months after surgery, no modification was observed for most tasks. The information processing speed tended to improve. There was a significant reduction of the performance in a delayed free recall test and a trend toward a significant reduction of categorial word fluency. At one year after surgery, most task measures did not change. Slight impairment was observed for tasks evaluating executive function. Examination of individual results showed that some patients (30% at 3 months after surgery) showed an overall cognitive decline. Behavioural changes were also observed in 4 patients with overall cognitive decline in one of them. CONCLUSION: In general, STN deep brain stimulation can be considered as a significant contribution to the treatment of severe Parkinson's disease However, in some patients it can induce overall cognitive decline or behavioural changes.

Cognition Disorders↗

PubMed2004

The effectiveness of neurofeedback and stimulant drugs in treating AD/HD: part II. Replication.

This study replicated T. R. Rossiter and T. J. La Vaque (1995) with a larger sample, expanded age range, and improved statistical analysis. Thirty-one ADIHD patients who chose stimulant drug (MED) treatment were matched with 31 patients who chose a neurofeedback (EEG) treatment program. EEG patients received either office (n = 14) or home (n = 17) neurofeedback. Stimulants for MED patients were titrated using the Test of Variables of Attention (TOVA). EEG (effect size [ES] = 1.01-1.71) and MED (ES = 0.80-1.80) groups showed statistically and clinically significant improvement on TOVA measures of attention, impulse control, processing speed, and variability in attention. The EEG group demonstrated statistically and clinically significant improvement on behavioral measures (Behavior Assessment System for Children, ES = 1.16-1.78, and Brown Attention Deficit Disorder Scales, ES = 1.59). TOVA gain scores for the EEG and MED groups were not significantly different. More importantly, confidence interval and nonequivalence null hypothesis testing confirmed that the neurofeedback program produced patient outcomes equivalent to those obtained with stimulant drugs. An effectiveness research design places some limitations on the conclusions that can be drawn.

Adolescent↗

PubMed2007

Inhibitory control in children with autism spectrum disorder.

Impairments in executive abilities such as cognitive flexibility have been identified in individuals with autism spectrum disorder (ASD). It remains unclear, however, whether such individuals also experience impairments in another executive ability: inhibitory control. In the present study, we administered three inhibitory tasks to 18 children with ASD, 23 siblings of children with ASD, and 25 typically developing children. After controlling for individual differences in age, overall IQ, and processing speed, children with ASD demonstrated impaired performance on two of the three inhibitory tasks. Results suggest that children with ASD experience circumscribed deficits in some but not all aspects of inhibitory control. More generally, the findings underscore the importance of using multiple measures to assess a putative single cognitive ability.

Adolescent↗